Proteolytic surface functionalization enhances in vitro magnetic nanoparticle mobility through extracellular matrix
Proteolytic surface functionalization enhances in vitro magnetic nanoparticle mobility through extracellular matrix
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DOI：
10.1021/nl052241g
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发表时间：
2006-02-01
期刊：
影响因子：
10.8
通讯作者：
Giorgio, TD
中科院分区：
文献类型：
--
作者：
Kuhn, SJ;Finch, SK;Giorgio, TD
空间障碍，如I型胶原，极大地限制了以大分子和纳米颗粒(NP)为基础的治疗剂的间质输送。胶原酶连接的超顺磁性纳米粒克服了这些障碍，在磁场的影响下，以90mumh(-1)的速度通过了体外细胞外基质(ECM)，这一速度类似于侵袭细胞。NP在ECM中的迁移在5天内呈线性减少。胶原酶-NP结构克服了纳米和微米级治疗部署的两个最重要的障碍：通过将蛋白水解酶固定在NP表面，在临床有用的时间范围内保持了蛋白水解酶的稳定性，并通过结合的微生物蛋白酶降解了组织生物分布的间质屏障。
Steric barriers such as collagen I sharply limit interstitial delivery of macromolecular and nanoparticle (NP) based therapeutic agents. Collagenase-linked superparamagnetic NPs overcame these barriers and moved through in vitro extracellular matrix (ECM) at 90 mu m h(-1), a rate similar to invasive cells, under the influence of a magnetic field. NP migration in ECM diminished linearly over 5 days. The collagenase-NP construct overcame two of the most significant barriers to nano- and microscale therapeutics deployment: proteolytic enzyme stability was maintained during a clinically useful time frame by immobilization on the NP surface and degradation of interstitial barriers to tissue biodistribution was enabled by the conjugated microbial protease.